Nutrient-Induced Metabolic Stress, Adaptation, Detoxification, and Toxicity in the Pancreatic β-Cell DOI Open Access

Marc Prentki,

Marie‐Line Peyot,

Pellegrino Masiello

et al.

Diabetes, Journal Year: 2020, Volume and Issue: 69(3), P. 279 - 290

Published: Feb. 13, 2020

Paraphrasing the Swiss physician and father of toxicology Paracelsus (1493-1541) on chemical agents used as therapeutics, "the dose makes poison," it is now realized that this aptly applies to calorigenic nutrients. The case here pancreatic islet β-cell presented with excessive levels nutrients such glucose, lipids, amino acids. short-term effects these exert are enhanced insulin biosynthesis secretion changes in glucose sensitivity. However, chronic fuel surfeit triggers additional compensatory adaptive mechanisms by β-cells cope increased demand or protect itself. When fail, toxicity due nutrient surplus ensues, leading dysfunction, dedifferentiation, apoptosis. terms glucotoxicity, lipotoxicity, glucolipotoxicity have been widely used, but there some confusion what they mean precisely which most appropriate for a given situation. Here we address gluco-, lipo-, glucolipo-toxicities assessing evidence both against each them. We also discuss potential defend view many identified "toxic" excess, may include acids, fact beneficial processes. In addition, candidate fuel-excess detoxification pathways evaluated. Finally, propose more general term should be vivo situation overweight-associated type 2 diabetes reflecting toxic processes mixed excess: "nutrient-induced metabolic stress" or, brief, "nutri-stress."

Language: Английский

A guide to the organ-on-a-chip DOI Creative Commons
Chak Ming Leung, Pim de Haan, Kacey Ronaldson-Bouchard

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: May 12, 2022

Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering microfabrication, OoCs have gained interest as a next-generation experimental platform investigate pathophysiology effect of therapeutics body. There many examples there applications, making it difficult for new researchers understand what makes one OoC more suited an application than another. This Primer is intended give introduction aspects that need be considered when developing application-specific OoC. The covers guiding principles considerations design, fabricate operate OoC, well subsequent assaying techniques extract biological information from devices. Alongside this discussion current future applications technology, inform design operational decisions during implementation systems. with aim mimicking physiology range biomedical therapeutic applications. Leung, de Haan et al. report practical tips organ-on-a-chip

Language: Английский

Citations

616

Obesity and cardiovascular disease: revisiting an old relationship DOI
Chrysi Koliaki, Stavros Liatis, Alexander Kokkinos

et al.

Metabolism, Journal Year: 2018, Volume and Issue: 92, P. 98 - 107

Published: Nov. 3, 2018

Language: Английский

Citations

583

Risk of diabetes-associated diseases in subgroups of patients with recent-onset diabetes: a 5-year follow-up study DOI
Oana‐Patricia Zaharia, Klaus Straßburger, Alexander Strom

et al.

The Lancet Diabetes & Endocrinology, Journal Year: 2019, Volume and Issue: 7(9), P. 684 - 694

Published: July 22, 2019

Language: Английский

Citations

471

The aetiology and molecular landscape of insulin resistance DOI
David E. James,

Jacqueline Stöckli,

Morris J. Birnbaum

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(11), P. 751 - 771

Published: July 20, 2021

Language: Английский

Citations

445

Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications DOI
Jun Ren, Ne N. Wu, Shuyi Wang

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1745 - 1807

Published: May 5, 2021

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to rapidly increased overweight obesity. To this point, epidemiological, clinical, experimental evidence supports existence unique disease entity termed "obesity cardiomyopathy," which develops independent hypertension, coronary disease, other diseases. Our contemporary review evaluates for pathological condition, examines putative responsible mechanisms, discusses therapeutic options disorder. Clinical findings have consolidated presence left ventricular dysfunction Experimental investigations uncovered pathophysiological changes myocardial structure function genetically predisposed diet-induced Indeed, consolidates wide array cellular molecular mechanisms underlying etiology obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover free fatty acids, lipotoxicity, amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, fibrosis, dampened flow reserve, microvascular (microangiopathy), endothelial impairment. Given important role risk failure, that with preserved systolic recent rises COVID-19-associated cardiovascular mortality, should provide compelling cardiomyopathy, various comorbid conditions, offer new insights into potential approaches (pharmacological lifestyle modification) clinical management cardiomyopathy.

Language: Английский

Citations

253

Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors DOI
Sven Francque, Gyöngyi Szabó, Manal F. Abdelmalek

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 18(1), P. 24 - 39

Published: Oct. 22, 2020

Language: Английский

Citations

246

The crucial role and mechanism of insulin resistance in metabolic disease DOI Creative Commons
Xuefei Zhao, Xuedong An,

Cunqing Yang

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 28, 2023

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, nonalcoholic fatty liver disease, provides basis for common understanding these chronic diseases. In this study, we provide systematic review causes, mechanisms, treatments IR. The pathogenesis IR depends on genetics, obesity, age, drug effects. Mechanistically, any factor leading to abnormalities insulin signaling pathway leads host, including receptor abnormalities, disturbances internal environment (regarding inflammation, hypoxia, lipotoxicity, immunity), metabolic function organelles, other abnormalities. available therapeutic strategies are mainly exercise dietary habit improvement, chemotherapy based biguanides glucagon-like peptide-1, traditional Chinese medicine (e.g., herbs acupuncture) can also be helpful. Based current there still some vacancies follow up consider, is need define more precise biomarkers different lifestyle interventions, explore natural or synthetic drugs targeting treatment. This could enable treatment patients with multiple combined diseases, aim treating disease holistically reduce healthcare expenditures improve quality life extent.

Language: Английский

Citations

222

Mitochondrial alterations in fatty liver diseases DOI Creative Commons
Bernard Fromenty, Michael Roden

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 78(2), P. 415 - 429

Published: Oct. 7, 2022

Fatty liver diseases can result from common metabolic diseases, as well xenobiotic exposure and excessive alcohol use, all of which have been shown to exert toxic effects on hepatic mitochondrial functionality dynamics. Invasive or complex methodology limits large-scale investigations mitochondria in human livers. Nevertheless, abnormal function, such impaired fatty acid oxidation oxidative phosphorylation, drives stress has identified an important feature steatohepatitis. On the other hand, be flexible adapt ambient condition prevent triglyceride lipotoxin accumulation obesity. Experience studies xenobiotics provided insights into regulation mitochondria. Increasing awareness joint presence disease-related (lipotoxic) alcohol-related further highlights need better understand their mutual interaction potentiation disease progression. Recent clinical assessed diets bariatric surgery mitochondria, are also evolving interesting therapeutic target non-alcoholic disease. This review summarises current knowledge with a focus linked obesity, type 2 diabetes xenobiotics.

Language: Английский

Citations

215

High-fat diet promotes renal injury by inducing oxidative stress and mitochondrial dysfunction DOI Creative Commons
Yue Sun, Xin Ge, Xue Li

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(10)

Published: Oct. 24, 2020

Abstract Obesity has been recognized as a major risk factor for chronic kidney disease, but the underlying mechanism remains elusive. Here, we investigated whereby long-term high-fat diet (HFD) feeding induces renal injury in mice. The C57BL/6 mice fed HFD 16 weeks developed obesity, diabetes, and dysfunction manifested by albuminuria blood accumulation of BUN creatinine. HFD-fed showed marked glomerular tubular injuries, including prominent defects filtration barrier increased cell apoptosis. Mechanistically, markedly triglyceride cholesterol contents activated lipogenic pathways synthesis. also oxidative stress induced mitochondrial fission cells, thereby activating pro-apoptotic pathway. In HK-2 mesangial cultures, high glucose, fatty acid, TNF-α combination was able to activate pathways, increase stress, promote fission, pathway, all which could be attenuated an inhibitor that depleted reactive oxygen species. Taken together, these observations suggest causes at least part result tissue lipid accumulation, dysfunction, excess programmed death.

Language: Английский

Citations

210

Mitophagy in human health, ageing and disease DOI
Anna Picca, Julie Faitg, Johan Auwerx

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(12), P. 2047 - 2061

Published: Nov. 30, 2023

Language: Английский

Citations

185